Prevalence of mutations and functional analyses of melanocortin 4 receptor variants identified among 750 men with juvenile-onset obesity

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Prevalence of mutations and functional analyses of melanocortin 4 receptor variants identified among 750 men with juvenile-onset obesity. / Larsen, Lesli H; Echwald, Søren Morgenthaler; Sørensen, Thorkild I A; Andersen, Teis; Wulff, Birgitte S; Pedersen, Oluf.

In: The Journal of Clinical Endocrinology & Metabolism, Vol. 90, No. 1, 2005, p. 219-224.

Research output: Contribution to journalJournal articleResearchpeer-review

Harvard

Larsen, LH, Echwald, SM, Sørensen, TIA, Andersen, T, Wulff, BS & Pedersen, O 2005, 'Prevalence of mutations and functional analyses of melanocortin 4 receptor variants identified among 750 men with juvenile-onset obesity', The Journal of Clinical Endocrinology & Metabolism, vol. 90, no. 1, pp. 219-224. https://doi.org/10.1210/jc.2004-0497

APA

Larsen, L. H., Echwald, S. M., Sørensen, T. I. A., Andersen, T., Wulff, B. S., & Pedersen, O. (2005). Prevalence of mutations and functional analyses of melanocortin 4 receptor variants identified among 750 men with juvenile-onset obesity. The Journal of Clinical Endocrinology & Metabolism, 90(1), 219-224. https://doi.org/10.1210/jc.2004-0497

Vancouver

Larsen LH, Echwald SM, Sørensen TIA, Andersen T, Wulff BS, Pedersen O. Prevalence of mutations and functional analyses of melanocortin 4 receptor variants identified among 750 men with juvenile-onset obesity. The Journal of Clinical Endocrinology & Metabolism. 2005;90(1):219-224. https://doi.org/10.1210/jc.2004-0497

Author

Larsen, Lesli H ; Echwald, Søren Morgenthaler ; Sørensen, Thorkild I A ; Andersen, Teis ; Wulff, Birgitte S ; Pedersen, Oluf. / Prevalence of mutations and functional analyses of melanocortin 4 receptor variants identified among 750 men with juvenile-onset obesity. In: The Journal of Clinical Endocrinology & Metabolism. 2005 ; Vol. 90, No. 1. pp. 219-224.

Bibtex

@article{4c0878f074c311dbbee902004c4f4f50,
title = "Prevalence of mutations and functional analyses of melanocortin 4 receptor variants identified among 750 men with juvenile-onset obesity",
abstract = "Mutations in the gene encoding the melanocortin 4 receptor (MC4R) are associated with the most common monogenic form of obesity. We examined 750 Danish men with juvenile-onset obesity (body mass index 33.3 +/- 2.4 kg/m(2)) and 706 control subjects (body mass index 21.4 +/- 2.1 kg/m(2)) for mutations in MC4R. A total of 14 different mutations were identified of which two, Ala219Val and Leu325Phe, were novel variants. The variant receptor, Leu325Phe, was unable to bind [Nle4,d-Phe7]-alphaMSH, whereas the Ala219Val variant showed a significantly impaired melanotan II induction of cAMP, compared with the wild-type receptor. The remaining 11 mutations have previously been reported, but selected MC4R variants were further characterized in vitro in the present study. A previously identified nonsense mutation, Tyr35stop, had a relatively high allele frequency (0.6{\%}), suggesting a possible founder effect in the Danish population. This study shows a carrier frequency of 2.5{\%} of pathogenic mutations in the MC4R gene in a population-based study of obese men. Thus, variation in this gene is the most common known specific genetic cause of obesity among Scandinavian men.",
keywords = "Adult, Cohort Studies, Humans, Male, Mutation, Obesity, Receptor, Melanocortin, Type 4",
author = "Larsen, {Lesli H} and Echwald, {S{\o}ren Morgenthaler} and S{\o}rensen, {Thorkild I A} and Teis Andersen and Wulff, {Birgitte S} and Oluf Pedersen",
year = "2005",
doi = "10.1210/jc.2004-0497",
language = "English",
volume = "90",
pages = "219--224",
journal = "Journal of Clinical Endocrinology and Metabolism",
issn = "0021-972X",
publisher = "Oxford University Press",
number = "1",

}

RIS

TY - JOUR

T1 - Prevalence of mutations and functional analyses of melanocortin 4 receptor variants identified among 750 men with juvenile-onset obesity

AU - Larsen, Lesli H

AU - Echwald, Søren Morgenthaler

AU - Sørensen, Thorkild I A

AU - Andersen, Teis

AU - Wulff, Birgitte S

AU - Pedersen, Oluf

PY - 2005

Y1 - 2005

N2 - Mutations in the gene encoding the melanocortin 4 receptor (MC4R) are associated with the most common monogenic form of obesity. We examined 750 Danish men with juvenile-onset obesity (body mass index 33.3 +/- 2.4 kg/m(2)) and 706 control subjects (body mass index 21.4 +/- 2.1 kg/m(2)) for mutations in MC4R. A total of 14 different mutations were identified of which two, Ala219Val and Leu325Phe, were novel variants. The variant receptor, Leu325Phe, was unable to bind [Nle4,d-Phe7]-alphaMSH, whereas the Ala219Val variant showed a significantly impaired melanotan II induction of cAMP, compared with the wild-type receptor. The remaining 11 mutations have previously been reported, but selected MC4R variants were further characterized in vitro in the present study. A previously identified nonsense mutation, Tyr35stop, had a relatively high allele frequency (0.6%), suggesting a possible founder effect in the Danish population. This study shows a carrier frequency of 2.5% of pathogenic mutations in the MC4R gene in a population-based study of obese men. Thus, variation in this gene is the most common known specific genetic cause of obesity among Scandinavian men.

AB - Mutations in the gene encoding the melanocortin 4 receptor (MC4R) are associated with the most common monogenic form of obesity. We examined 750 Danish men with juvenile-onset obesity (body mass index 33.3 +/- 2.4 kg/m(2)) and 706 control subjects (body mass index 21.4 +/- 2.1 kg/m(2)) for mutations in MC4R. A total of 14 different mutations were identified of which two, Ala219Val and Leu325Phe, were novel variants. The variant receptor, Leu325Phe, was unable to bind [Nle4,d-Phe7]-alphaMSH, whereas the Ala219Val variant showed a significantly impaired melanotan II induction of cAMP, compared with the wild-type receptor. The remaining 11 mutations have previously been reported, but selected MC4R variants were further characterized in vitro in the present study. A previously identified nonsense mutation, Tyr35stop, had a relatively high allele frequency (0.6%), suggesting a possible founder effect in the Danish population. This study shows a carrier frequency of 2.5% of pathogenic mutations in the MC4R gene in a population-based study of obese men. Thus, variation in this gene is the most common known specific genetic cause of obesity among Scandinavian men.

KW - Adult

KW - Cohort Studies

KW - Humans

KW - Male

KW - Mutation

KW - Obesity

KW - Receptor, Melanocortin, Type 4

U2 - 10.1210/jc.2004-0497

DO - 10.1210/jc.2004-0497

M3 - Journal article

VL - 90

SP - 219

EP - 224

JO - Journal of Clinical Endocrinology and Metabolism

JF - Journal of Clinical Endocrinology and Metabolism

SN - 0021-972X

IS - 1

ER -

ID: 90267